Journal
CLINICAL AND EXPERIMENTAL ALLERGY
Volume 34, Issue 9, Pages 1474-1479Publisher
BLACKWELL PUBLISHING LTD
DOI: 10.1111/j.1365-2222.2004.02066.x
Keywords
airway innervation; jugular-nodose ganglia; mouse; nerve growth factor; neurotrophin; tachykinin; tyrosine kinase receptor trkA; vanilloid receptor-1 (TRPV1 or VR1)
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Background Nerve growth factor (NGF) is elevated in allergic diseases such as bronchial asthma and can lead to an induction of substance P (SP) and related neuropeptides in guinea-pigs large-diameter, neurofilament-positive airway neurons. Objective In the present study, the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV1 expression in airway-specific vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) of mice was investigated. Methods Using retrograde neuronal tracing in combination with double-labelling immunohistochemistry, SP, trkA- and TRPV1-receptor expression was examined in airway-specific sensory neurons of BALB/c mice before and after NGF treatment. Results NGF injected into the lower airway was able to induce SP (13.0+/-2.03% vs. 5.9+/-0.33%) and trkA expression (78+/-2.66% vs. 60+/-2.11%) in larger diameter (>25 mum), capsaicin-insensitive and trkA-positive vagal sensory neurons that were retrograde-labelled with Fast Blue dye from the main stem bronchi. Conclusion Based on the extent of SP and trkA co-expression in airway-specific neurons by NGF treatment, the present study suggests that, following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation, there may be trkA-mediated SP induction to mediate neurogenic airway inflammation.
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